In nearly all eukaryotic cells, calcium (Ca.sup.2+) functions as an intracellular signaling molecule in diverse cellular processes including cell proliferation, neurotransmitter secretion, glycogen metabolism, and skeletal muscle contraction. Within a resting cell, the concentration of Ca.sup.2+ in the cytosol is extremely low, &lt;10.sup.-7 M. However, when the cell is stimulated by an external signal, such as a neural impulse or a growth factor, the cytosolic concentration of Ca.sup.2+ increases by about 50-fold. This influx of Ca.sup.2+ is caused by the opening of plasma membrane Ca.sup.2+ channels and the release of Ca.sup.2+ from intracellular stores such as the endoplasmic reticulum. Ca.sup.2+ directly activates regulatory enzymes, such as protein kinase C, which trigger signal transduction pathways. Ca.sup.2+ also binds to specific Ca.sup.2+ -binding proteins (CBPs) such as calmodulin (CaM) which then activate multiple target proteins including enzymes, membrane transport pumps, and ion channels. CaM is the most widely distributed and the most common mediator of calcium effects and appears to be the primary sensor of Ca.sup.2+ changes in eukaryotic cells. The binding of Ca.sup.2+ to CaM induces marked conformational changes in the protein permitting interaction with, and regulation of over 100 different proteins. CaM interactions are involved in a multitude of cellular processes including, but not limited to, gene regulation, DNA synthesis, cell cycle progression, mitosis, cytokinesis, cytoskeletal organization, muscle contraction, signal transduction, ion homeostasis, exocytosis, and metabolic regulation (Celio, M. R. et al. (1996) Guidebook to Calcium-binding Proteins, Oxford University Press, Oxford, UK, pp. 15-20).
A novel mouse gene named MO25, expressed during early stages of development, has recently been identified and is believed to encode a CBP. The Drosophila equivalent of MO25, DMO25, encodes a polypeptide of 339 amino acid residues with a calculated molecular mass of 39.3 kDa. The novel CBP was found to be conserved among Drosophila, mouse, and yeast. In particular, the carboxy-terminal region of the protein is highly conserved among these species. A homology search revealed that the amino acid sequence of MO25 and DMO25 is similar to a protein encoded in an open reading frame near the calcineurin B subunit gene on chromosome XI in Saccharomyces cerevisiae. Calcineurin B is the small Ca.sup.2+ -binding regulatory subunit of calcineurin, a CaM-regulated protein phosphatase. The conservation of the MO25 and DMO25 gene structure among species and the wide tissue expression profile indicates that the function of the gene is likely to be fundamental in many cell types as well as during development (Nozaki, M. et al. (1996) DNA Cell Biol. 15:505-509; and Miyamoto, H. et al. (1993) Mol. Reprod. Dev. 34:1-7).
CBPs are implicated in a variety of disorders. For example, calcineurin is found in the cells of all eukaryotes ranging from yeast to mammals. Calcineurin is a target for inhibition by the immunosuppressive agents cyclosporin A and FK506 emphasizing its importance in immune disorders (Kissinger, C. R. et al. (1995) Nature 378:641-644). Calcineurin also plays a critical role in transcriptional regulation and growth control in T-lymphocytes (Wang, M. G. et al. (1996) Cytogenet. Cell Genet. 72:236-241). Additionally, levels of CaM are increased several-fold in tumors and tumor-derived cell lines for various types of cancer (Rasmussen, C. D. and Means, A. R. (1989) Trends in Neuroscience 12:433-438). Calcium binding S100.beta. is another example of a CBP involved in a variety of disorders. S100.beta. contains an EF-hand motif and is abundantly expressed in the nervous system. S100.beta. levels are increased in the blood and cerebrospinal fluid of patients with neurological injury resulting from cerebral infarction, transient ischemic attacks, hemorrhagia, head trauma, and Down's syndrome. Furthermore, S100.beta. and other neural-specific CBPs may also protect against neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases.
The discovery of a new calcium binding protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of cancer, reproductive disorders, immune disorders, and developmental disorders.